Rosuvastatin, which is an antihyperchlolesterolemic drug, is chemically known as (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoic acid calcium (2:1) salt of Formula I.
Rosuvastatin is enantiomerically pure compound having two chiral centers in the side chain of the molecule. All four isomers of Rosuvastatin can be separated by HPLC.
The synthetic process for preparing Rosuvastatin Calcium is disclosed in U.S. Pat. No. RE 37,314 E, which involves reduction of 5-keto-3(R)-hydroxy Rosuvastatin methyl ester using sodium borohydride and diethylmethoxyborane in presence of tetrahydrofuran and methanol.
WO 2005/042522 A 1 discloses crystalline compound of ethyl-(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl] (3R,5S)-3,5-dihydroxyhept-6-enoate having an X-ray powder diffraction pattern with peaks at 2-theta 4.3, 8.1, 11.3, 12.4, 15.1, 19.9, 21.0, 21.7, 22.1 and 23.5. The process is as summarized below:

WO 2006/100689 A1 discloses a process to prepare Rosuvastatin alkyl ester from Rosuvastatin keto ester by combining Rosuvastatin keto ester, diethylmethoxy borane in tetrahydrofuran and methanol. Thereafter, sodium borohydride was added to the above reaction mass and stirred to obtain Rosuvastatin alkyl ester. HPLC analysis of the Rosuvastatin alkyl ester produced by the method disclosed above revealed that the reduction did not go to completion and the resulting Rosuvastatin alkyl ester is contaminated with unreacted starting material and also high level of diastereomeric impurity. It is tedious to separate these impurities by the conventional purification techniques. Therefore, we realized that there is a need for reduction, which gives pure Rosuvastatin alkyl ester.
WO 2007/040940 A1 discloses a process to prepare Rosuvastatin alkyl ester from Rosuvastatin keto ester by combining MeO-9-BBN or diethylmethoxyborane with an organic solvent selected from a group consisting of methylene chloride, toluene, methyl t-butyl ether, diethyl ether, tetrahydrofuran, dioxane, methanol, ethanol, isopropanol, n-butanol; and a source of hydride ion and then adding to the said combination to a solution of a Rosuvastatin keto ester in an organic solvent to obtain a reaction mixture. Thereafter, the reaction mixture was maintained to obtain Rosuvastatin alkyl ester. Analysis of the product obtained by the above process revealed that the presence of unreacted starting material in the product, which was difficult to separate by normal crystallization techniques.
Therefore, we report herein a new crystalline form of Rosuvastatin ethyl ester and also a process to prepare Rosuvastatin alkyl esters having low level of diastereomeric impurity and other impurities, which can give Rosuvastatin calcium with desired quality.